Evaluating Glucocorticoid-Related Damage in Elderly Patients With ANCA-Associated Vasculitis

A reduced initial glucocorticoid dose with rapid reduction may improve the safety of glucocorticoid treatment in elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), according to study results published in Arthritis Research & Therapy.

Glucocorticoid treatment for AAV can improve disease prognosis, but it may cause chronic damage because of the high incidence of chronic conditions, including diabetes, osteoporosis, cataracts, and hypertension, in elderly patients. The current study aimed at assessing treatment-related damage in patients with elderly-onset AAV.

Using data from 2 nationwide prospective inception cohort studies (RemIT-JAV, an observational cohort study of remission induction therapy in Japanese patients with AAV and RemIT-JAV-RPGN, an observational cohort study of remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis), the researchers enrolled patients with newly diagnosed, elderly-onset (≥75 years) AAV with available data on glucocorticoid dose.

The primary outcome was 12-month treatment-related Vasculitis Damage Index (VDI), defined as osteoporosis, diabetes, cataracts, atrophy and weakness, malignancy, gonadal failure, marrow failure, chemical cystitis, avascular necrosis, hypertension, angina/coronary artery disease, alopecia, cerebrovascular accident, myocardial disease, and mouth ulcers.

Researchers included 179 eligible patients (mean age, 80.0 years; 62% women) with available data on glucocorticoid dose and 12-month VDI score. Patients were divided into 3 groups, according to initial glucocorticoid daily dose: high-dose, prednisolone 0.8 mg/kg or more (n=65); medium-dose, 0.6 less than or equal to prednisolone less than 0.8 mg/kg (n=52); and low-dose, prednisolone less than 0.6 mg/kg (n=59). Compared with patients in the other groups, those in the low-dose group were older and had higher serum creatinine levels.

At 12 months, there were no statistically significant differences in remission rates between the patients in the low-, medium-, and high-dose prednisolone groups (85%, 79%, and 88% of patients, respectively; P =.38). Similarly, relapse rates were not significantly different between the groups (10%, 12%, and 12%, respectively; P =.93). However, serious infections were more common among patients who received high-dose vs low- or medium-dose prednisolone (43% vs 22% and 19%, respectively; P =.0007).

At 12 months, total VDI score was not statistically significant different between patients who received a low, medium, or high dose of prednisolone (2.65, 2.40, and 2.25, respectively; P =.57). Treatment-related VDI scores were also not statistically significant between the groups (0.91, 0.45, and 0.77, respectively; P =.14).

Logistic regression analysis revealed that concomitant cyclophosphamide usage was associated with a reduced risk of developing diabetes (odds ratio [OR], 0.29; P =.027), but daily prednisolone dose at 12 months was an independent predictor of diabetes (OR, 1.14; P =.045).

The study had several limitations, including onsite investigator discretion with selecting treatment strategy, potential underestimation of the outcomes, and lack of a validation study. In addition, a majority of patients were tested myeloperoxidase (MPO)-ANCA-positive, therefore, the results of the study may not be applicable to elderly patients with proteinase 3 (P3)-ANCA.

“Rapidly reducing the initial [glucocorticoid] dose to [prednisolone] [less than] 0.8 mg/kg/day perhaps is required to ensure the safe treatment of elderly patients with AAV,” the researchers concluded.

Reference

Sada K-E, Ohashi K, Asano Y, et al. Treatment-related damage in elderly-onset ANCA-associated vasculitis: safety outcome analysis of two nationwide prospective cohort studies. Arthritis Res Ther. 2020;;22(1):236.